Henry S. Kaplan Distinguished Scientist Award Lecture 2007. The remarkable yin and yang of tumour hypoxia.

PURPOSE: To honour perhaps the most influential man in the radiation sciences, Henry S. Kaplan, by reviewing the field of tumour hypoxia, one of his many interests.
RESULTS: It was postulated over 50 years ago by Thomlinson and Gray that human solid tumours would contain hypoxic cells and that they would exert a negative influence on the outcome of radiotherapy, a prediction that has been amply validated. In addition to the 'chronic' hypoxia that they proposed we know that tumours also have 'acute' hypoxia produced by the unstable nature of tumour blood flow. The most hypoxic cells in the tumour are the key mediators of the response to large radiation doses (such as are given in stereotactic body radiotherapy), whereas cells at intermediate levels of hypoxia are the most important for standard fractionated radiotherapy. But tumour hypoxia can be exploited to preferentially activate anti-cancer drugs such as tirapazamine in tumours. In addition, hypoxia, through the transcription factor hypoxia inducible factor 1(HIF-1), drives both local angiogenesis and vasculogenesis from circulating cells. We have shown that local tumour irradiation can inhibit angiogenesis, making growth of tumours from surviving cancer cells dependent on vasculogenesis, and that inhibiting key steps in vasculogenesis can markedly sensitize tumours to irradiation.